Triethylamine → (+)-1-[1-(2-toluoylmethyl)-2-oxo-5-(3,3-dimethylbutanoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-benzyloxycarbonylphenyl)urea

Participants

Reaction Steps

Diphenylphosphoryl azide (6.60 g) and triethylamine (3.75 g) were added to a solution of isophthalic acid benzyl ester (5.38 g) in anhydrous dioxane (50 ml), and the mixture was stirred at internal temperature 60° for 30 minutes and stirred at internal temperature 80° for one hour. The reaction mixture was allowed to cool at room temperature,a solution of (+)-1-(2-toluoylmethyl)-2-oxo-3-amino-5-(3,3-dimethylbutanoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (3.0 g) in anhydrous dioxane (50 ml) was added thereto, and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was concentrated under reduced pressure, chloroform (200 ml) was added to the residue, the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography(NH-DM1020, produced by Fujisilicia Co. Ltd., n-hexane:ethyl acetate=2:1), to thereby obtain 4.08 g of the title compound (Yield 85.2%).

Provenance & Evidence